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Cardiovascular Research 2005 65(1):195-202; doi:10.1016/j.cardiores.2004.10.001
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Copyright © 2004, European Society of Cardiology

Cardiac reporter gene imaging using the human sodium/iodide symporter gene

Masao Miyagawaa,1, Moritz Beyera,1, Bettina Wagnera, Martina Antonb, Christine Spitzwegc, Bernd Gansbacherb, Markus Schwaigera and Frank M. Bengela,*

aNuklearmedizinische Klinik und Poliklinik, Technische Universität München, Klinikum rechts der Isar, Ismaninger Str. 22, 81675 München, Germany
bInstitut für Experimentelle Onkologie und Therapieforschung, Technische Universität München, Munich, Germany
cMedizinische Klinik II, Ludwig Maximilians Universität München, Munich, Germany

* Corresponding author. Tel.: +49 89 4140 2971; fax: +49 89 4140 4950. Email address: frank.bengel{at}lrz.tum.de

Objective: Imaging of reporter gene expression holds promise for noninvasive monitoring of cardiovascular molecular therapy. We investigated the feasibility of myocardial gene expression imaging in living rats using the human sodium/iodide symporter gene (hNIS) and widely available scintigraphic techniques.

Methods: We injected adenovirus expressing hNIS under control of cytomegalovirus promoter (AdhNIS) directly into left ventricular myocardium of Wistar rats. For detection of reporter gene expression, dynamic gamma-camera imaging was performed following intravenous injection of 123Iodide or 99mTechnetium.

Results: For both radiotracers, focal cardiac accumulation was identified as early as 10 min, and remained detectable until 2 hrs after injection, while it was not present in animals injected with LacZ control virus. Intensity of tracer accumulation gradually decreased when decreasing titers of AdhNIS were applied. Treatment with sodium perchlorate (a blocker of hNIS) abolished cardiac tracer uptake after AdhNIS-infection. Serial imaging after cardiac gene transfer demonstrated a peak of tracer signal between days 1 and 3, and a subsequent decrease until day 12. Postmortem analysis of hearts yielded significant correlation between in vivo radiotracer accumulation and ex vivo gamma-counting. Autoradiography demonstrated specific regional radioactivity in AdhNIS-infected myocardial areas.

Conclusions: hNIS offers a practical and reliable approach for myocardial gene expression imaging. Using suitable vectors, hNIS may be coexpressed with therapeutic genes or stably expressed in stem cells for future monitoring of cardiovascular molecular therapy.

KEYWORDS Radionuclides; Cardiac imaging; Gene expression; Gene therapy; Reporter genes; Sodium/iodide transporter

1 Both authors (MM and MB) contributed equally to this work.

Time for primary review 17 days


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